Journal of Microbial & Biochemical Technology

NAD(H)-linked methylglyoxal oxidoreductase regulates cellular methylglyoxal and pyruvate through enhanced activities of alcohol dehydrogenase and methylglyoxal-oxidizing enzymes in glutathione-depleted Candida albicans

Joint Event on 4^th World Congress and Expo on Applied Microbiology & 2^nd International Conference on Food Microbiology

November 29-December 01, 2017 Madrid, Spain

Min-Kyu Kwak

Sungkyul University, Republic of Korea

Scientific Tracks Abstracts: J Microb Biochem Technol

Abstract:

High methylglyoxal content disrupts cell physiology, but mammals have scavengers to prevent glycolytic and mitochondrial dysfunctions. In yeast, methylglyoxal accumulation triggers methylglyoxal-oxidizing alcohol dehydrogenase (ADH1) activity. While methylglyoxal reductases and glyoxalases have been well studied in prokaryotes and eukaryotes, experimental evidence for methylglyoxal dehydrogenase (Mgd) and other catalytic activities of this enzyme affecting glycolysis and the tricarboxylic acid cycle is lacking. A glycine-rich cytoplasmic Mgd protein, designated as Mgd1/Grp2, was isolated from glutathione-depleted Candida albicans. The effects of Mgd1/Grp2 activities on metabolic pathophysiology were investigated using knockout and overexpression mutants. We measured glutathione-(in)dependent metabolite contents and metabolic effects, including viability, oxygen consumption, ADH1 transcripts, and glutathione reductase and α-ketoglutarate dehydrogenase activities in the mutants. Based on the findings, methylglyoxal-oxidizing proteins were monitored to determine effects of MGD1/GRP2 disruption on methylglyoxal-scavenging traits during glutathione deprivation. Methylglyoxal-oxidizing NAD(H)-linked Mgd1/Grp2 was found solely in glutathione auxotrophs, and it catalyzed the reduction of both methylglyoxal and pyruvate. MGD1/GRP2 disruptants showed growth defects, cell-cycle arrest, and methylglyoxal and pyruvate accumulation with mitochondrial impairment, regardless of ADH1 compensation. Other methylglyoxal-oxidizing enzymes were identified as key glycolytic enzymes with enhanced activity and transcription in MGD1/ GRP2 disruptants, irrespective of glutathione content. Failure of methylglyoxal and pyruvate dissimilation by Mgd1/Grp2 deficiency leads to poor glutathione-dependent redox regulation despite compensation by Adh1. This is the first report that multifunctional Mgd activities contribute to scavenging methylglyoxal and pyruvate to maintain metabolic homeostasis and the redox pool via glycolytic enzymes and ADH1 expression.

Biography :

Min-Kyu Kwak has completed his PhD at School of Biological Sciences, and Institute of Microbiology, Seoul National University, Republic of Korea. He has completed Postdoctoral studies from Seoul National University. He has been appointed as a Professor in Sungkul University in Korea and as a Visiting Professor in University of Malaysia in Sabah. He is an Editorial Board Member of Academy of Annals of Clinical Immunology and Microbiology and an organizer of the International Congress on Science and Technology. He has published more than 22 papers in international and national journals and proceedings, as first author and corresponding author. He also presented 13 kinds of Korea and international patents regarding cyclic dipeptides inhibitory to against multidrug-resistant bacteria, pathogenic fungi, and influenza A virus.